Varicosity with neurotransmitter vesicles •Fig. 14.6 Controlsystemsofsmoothmuscle.Inbothmultiunitsmoothmuscle(A)andsingleunitsmoothmuscle(B),neurallyreleasedtransmittersorcirculatingorlocallygeneratedhormonesorsignalingmoleculescaninducecontractionorrelaxationofthesmoothmuscle.Thecombinationofaneurotransmitter,hormone,ordrugwithspecificreceptorsactivatescontractionbyincreasingcellCa++ .Theresponseofthecellsdependsontheconcentrationofthetransmittersorhormonesatthecellmembraneandthenatureofthereceptorspresent.Hormoneconcentrationsdependondiffusiondistance,release,reuptake,andcatabolism.Consequently,cellslackingcloseneuromuscularcontactswillhavealimitedresponsetoneuralactivityunlesstheyareelectricallycoupledsothatdepolarizationistransmittedfromcelltocell.A,Multiunitsmoothmusclesresemblestriatedmusclesinthatthereisnoelectricalcouplingandneuralregulationisimportant.B,Single-unitsmoothmusclesarelikecardiacmuscle,andelectricalactivityispropagatedthroughoutthetissue.Mostsmoothmusclesprobablyliebetweenthetwoendsofthesingleunit–multiunitspectrum.C,Scanningmicrographofvaricosenervelyingoverratsmallintestinescalebar= 3µm.D,Fluorescentimageofcatecholaminesinsingleadrenergicaxoninguineapigmesentery.Scalebar= 10µm.E,Depictionofdistributionofsympatheticnerves(in black) invasculature.Sympatheticnervesareassociatedwithsmallarteries(SA),largearterioles(la),smallveins(SV),largevenules(lv),smallarterioles(sa),andterminalarterioles(TA).Capillaries(c),post-capillaryvenules(pcv),andsmallvenules(svl)appeartolacksympatheticinnervation.(C,FromBurnstockG:Autonomicneuralcontrolmechanisms.Withspecialreferencetotheairways.InKalinerMA,BarnesPJ(Eds.),TheAirways.NeuralControlinHealthandDisease,MarcelDekker,NewYork(1988),pp.1–22.D,FromChamleyJH,MarkGE,CampbellGR,BurnstockG.(1972)Sympatheticgangliainculture.I.Neurons.Z.Zellforsch.Mikrosk.Anat.135,287-314.) aThepredominanteffectofsympatheticstimulationissmoothmusclecontractioncausedbytheabundanceofα1-ARrelativetoβ2-ARinsmoothmuscle.bActivationofβ2-ARonsmoothmusclemodulatesthedegreeofsmoothmusclecontractionduringsympatheticstimulation.Therapeuticβ2-ARagonistsareimportantfortherelaxationofbronchialsmoothmuscleduringasthmaticattacks.cVascularsmoothmusclesarepoorlyinnervatedbytheparasympatheticsystem.Duringvagalstimulation,however,acetylcholine(ACh)canbecomeelevatedinthecoronarycirculationandresultincoronaryrelaxation(mediatedbybindingofAChtoendothelialcells).NotethatthiseffectofAChisindirectbecausebindingofAChtoendothelialcellsresultsinreleaseofthesmoothmusclerelaxantnitricoxidefromtheendothelialcells.Inregionsofthecoronarycirculationwithdamagedendothelium,bindingofAChtocoronarysmoothmusclecouldpromotecontraction(vasospasm;directeffect).dAvarietyofhormonescanelevateInsP3insmoothmuscleandtherebyresultinsmoothmusclecontraction.SuchhormonesincludeangiotensinII,vasopressin,andendothelin,alongwiththeneurotransmittersnorepinephrineandacetylcholine.Asnotedabove,however,eachhormone/transmitterbindstoaspecificreceptortype.eDuringperiodsofintensemuscularactivity,adenosinecanbereleasedfromtheworkingmuscle,diffusetotheneighboringvasculature,andpromotevasodilation.Thus,adenosineisactingasalocalfactortoincreasebloodflowtoaspecificregion(i.e.,workingmuscle).AR,adrenergicreceptor;EC,endothelialcell;InsP3,inositol1,4,5-trisphosphate;SMC,smoothmusclecell.